Background:To evaluate whether the extent of baseline acute prostate inflammation (API) and chronic prostate inflammation (CPI) was associated with risk of prostate cancer (PCa) at 2-year repeat prostate biopsy in a clinical trial with systematic biopsies independent of PSA.Methods:A retrospective analysis of 6065 men with a negative baseline biopsy in the reduction by dutasteride of PCa events (REDUCE) trial undergoing 2-year biopsy. API and CPI extent (percentage of cores involved) and PCa (present or absent) were assessed by central pathology. The association of baseline API and CPI with PCa at the 2-year biopsy was evaluated with logistic regression in uni- and multivariable analyses.Results:API extent was classified as absent or involving 1-25%, 26-50%, 51-75% and >75% cores in 5140 (85%), 742 (12%), 151 (2%), 17 (<1%) and 15 (<1%) cases, respectively. CPI extent was classified as absent or involving 1-25%, 26-50%, 51-75% and >75% cores in 1367 (22%), 2532 (42%), 1474 (24%), 397 (7%) and 295 (5%) cases, respectively. More extensive API was associated with younger age, lower PSA and lower prostate volume, while more extensive CPI was associated with older age, lower PSA and higher prostate volume (all P<0.01). In both uni- and multivariable analyses, API and CPI extent were associated with lower risk of PCa at the 2-year biopsy (both P<0.01).Conclusions:In a cohort of men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy, a greater extent of baseline API and CPI was independently associated with lower PCa risk.